Oxidative damage is widespread in the brain in Alzheimer's Disease (AD) and may be related to amyloid-beta (Abeta) toxicity. Clinical and epidemiological evidence suggests that antioxidants such as vitamin E and vitamin C may lower the risk of AD or delay clinical milestones. Indole-3-propionic acid (IPA) is a highly potent, naturally occurring antioxidant that also inhibits fibril formation by Abeta. The objectives of this proposal are to conduct a phase IB study of IPA in patients with AD to assess its safety and tolerability. In addition, levels of biological markers related to oxidative damage and to AD will be measured, to assess central and peripheral biological activity of IPA. A 12 week, double blind, placebo-controlled multi-center study will be conducted. Patients will be assigned in a 4:1 ratio to receive IPA (40 patients total) or an identical placebo (10 patients) and will receive treatment for 12 weeks. Treatment during the first 4 weeks will be a low dose, followed by 4 weeks of a medium dose and 4 weeks of a higher dose. The primary outcome measure will be safety, assessed by frequencies of clinical and biochemical adverse events. Secondary outcome measures will be changes in levels of biological markers in plasma (8,12-isoprostane-F2) and cerebrospinal fluid (8,1-isoprostane-F2, tau and Abeta42) from baseline to 12 weeks. Pharmacokinetic information will be assessed using measures of plasma and CSF levels of IPA in relation to doses of IPA. Pharmacokinetic information will be assessed using measures of plasma and CSF levels of IPA in relation to doses of IPA. Clinical measures of cognition (ADAScog) and function (ADCS-ADL) will be used as further assessments of safety or of possible beneficial short-term effects on AD.